Guidelines for the management of symptomatic sexually transmitted infections: web annex F: systematic review for syndromic management of the anorectal syndrome

JUNE 2021 GUIDELINES FOR THE MANAGEMENT OF SYMPTOMATIC SEXUALLY TRANSMITTED INFECTIONS WEB ANNEX F. SYSTEMATIC REVIEW FOR SYNDROMIC MANAGEMENT OF THE ANORECTAL SYNDROME JUNE 2021 WEB ANNEX F. SYSTEMATIC REVIEW FOR SYNDROMIC MANAGEMENT OF THE ANORECTAL SYNDROME GUIDELINES FOR THE MANAGEMENT OF SYMPTOMATIC SEXUALLY TRANSMITTED INFECTIONS Guidelines for the management of symptomatic sexually transmitted infections: Web Annex F. Systematic review for syndromic management of the anorectal syndrome ISBN 978-92-4-003483-9 (electronic version) © World Health Organization 2021 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/ licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. 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Systematic review for syndromic management of the anorectal syndrome. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris. Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/ about/licensing. Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third-party-owned component in the work rests solely with the user. General disclaimers. 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The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. This publication forms part of the WHO guideline entitled Guidelines for the management of symptomatic sexually transmitted infections. It is being made publicly available for transparency purposes and information, in accordance with the WHO handbook for guideline development, 2nd edition (2014). Design and layout by 400 Communications. iii CONTENTS 1. Introduction 1 2. Methods 2 3. Results 6 3.1 PRISMA flow chart for anorectal syndromes 6 3.2 Anorectal syndrome 7 3.3 Risk of Bias using QUADAS-2 15 4. References 16 5. Appendix A - Search Results 19 5.1 Anorectal syndromes 19 11. INTRODUCTION Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), continue to present significant health, social, and economic problems in the developing world, leading to considerable morbidity, mortality, and stigma. In under-resourced settings, the lack of adequate laboratory infrastructure and/or high prohibitive costs of diagnostics means that in many settings, STI management relies on syndromic management rather than aetiological diagnosis and management. In these settings, the detection of asymptomatic STIs is largely non-existent. Therefore, synthesizing the latest evidence for the performance of syndromic STI case management would help the World Health Organization (WHO) in their guideline recommendations for syndromic STI management, last updated in 2003.[1] To evaluate if there is still a role for syndromic STI management or whether STI diagnostics are critical for STI case management, we systematically reviewed the evidence for the performance of syndromic management of STIs. Specifically, we conducted reviews on the diagnostic accuracy and aetiologies of syndromic case management of genital ulcer, anorectal infection and lower abdominal pain. Our specific objectives were to review the flowcharts used for: • people presenting with genital ulcer disease to detect herpes simplex virus (HSV) or syphilis or lymphogranuloma venereum (LGV) or chancroid, or if no flowcharts found, a minor review of test accuracy of different tests, or risk association/prevalence. • people presenting with the anorectal syndrome to detect anal STIs or if no flowcharts found, a major review of test accuracy of different tests, or risk association/prevalence. • people presenting with lower abdominal pain to detect pelvic inflammatory disease (PID) or vaginal or cervical infections, or if no flowcharts found, a major review of test accuracy of different tests, or risk association/prevalence. 2Study inclusion • Clinical guidelines/algorithms – Flow charts for genital ulcer (for syphilis, HSV, LGV, chancroid), anorectal syndromes (for Ct/Ng/Mg/LGV/HSV/Tp/Donovanosis), lower abdominal pain (for PID, vaginal/cervical infections), and vaginal discharge • Randomized controlled trials • Observational studies • Report on at least one of: – Comparing syndromic case management against laboratory-confirmed STIs – Risk factor analysis of signs/symptoms associated with STI diagnoses and other risk factors associated with STI syndromes Study exclusion • Contains no original data i.e. systematic reviews/Letter/editorials/Commentaries/Book chapters – But can use these to identify other relevant primary studies • Qualitative research about outcomes • Duplicated results from another study • Laboratory studies about testing STI diagnostic performance • Studies restricting study population, e.g. men with urethritis, women with cervicitis Search method Three separate searches were conducted: one for each of the syndromes under investigation. We included papers that focused on other aspects of syndromic management (i.e. acceptability, feasibility, equity, resources) in addition to the accuracy or sensitivity of the syndromic management approach. The search for each syndrome has been constructed as below. • Concept 1: syndromic management • Concept 2: syndrome under investigation • Concept 3: diagnostic accuracy and sensitivity papers • Results group 1: concept 1 AND concept 2 AND concept 3 • Results group 2: (concept 1 AND concept 2) NOT Results group 1 2. METHODS 32. Methods A draft search strategy was compiled in the OvidSP Medline database by an experienced information specialist. The search strategy included strings of terms, synonyms and controlled vocabulary terms (where available). As the syndromic management approach was not introduced until 1996, the search was limited to papers published in 1995 or after. No other limits were added. This search strategy was refined with the project team until the results retrieved reflected the scope of the project. The agreed OvidSP Medline search was adapted for each database to incorporate database-specific syntax and controlled vocabularies. Full details of the search strings used for each database can be found in the appendix. A The following databases were searched on 12 and 13 September 2019. • Ovid SP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, 1946 to September 11, 2019 • OvidSP Embase, 1974 to 11 September 2019 • OvidSP Global Health, 1910 to week 35, 2019 • OvidSP Northern Light Life Sciences Conference Abstracts, 2010 to Week 34, 2019 • Ebsco CINAHL Plus, complete database • Ebsco Africa-Wide Information, complete database • Clarivate Analytics Web of Science Core Collection, consisting of the following databases: – Science Citation Index Expanded (SCI-EXPANDED), 1970 - present – Social Sciences Citation Index (SSCI), 1970 - present – Arts & Humanities Citation Index (A&HCI), 1975 - present – Conference Proceedings Citation Index - Science (CPCI-S), 1990 - present – Conference Proceedings Citation Index - Social Science & Humanities (CPCI-SSH), 1990 - present – Emerging Sources Citation Index (ESCI), 2015 – present • BIREME/PAHO/WHO Virtual Health Library LILACS, complete database All citations identified by our searches were imported into EndNote X9 software. Duplicates were identified and removed using the method described on the LAS blog.1 4 Web Annex F. Systematic review for syndromic management of the anorectal syndrome Data extraction We followed the guidelines in the Cochrane Handbook 5.1.[2] Three groups of two independent reviewers screened the title and abstracts of unduplicated papers. Discrepancies in screening were resolved by a third reviewer (JO). Each team extracted relevant data from deduplicated full publications. Risk of bias assessment was conducted using the Joanna Briggs Institute Checklist for diagnostic studies.[3] Statistical analysis Diagnostic accuracy cannot be summarized by one measure as sensitivity and specificity are correlated. Therefore, we must choose hierarchical (multilevel) models that use a binomial data structure, i.e. we use a hierarchical logistic regression model in STATA 13.1. After pooling the studies, we report the sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio. The inverse of the negative likelihood ratio (1/LR-) can be used to compare with the positive likelihood ratio to indicate whether the positive or negative test result has a greater impact on the odds of disease. Likelihood ratios assess the probability or likelihood that the test result obtained would be expected in a person with the condition, compared to the probability or likelihood that the same result would be seen in a person without the condition. The positive likelihood ratio LR+ sensitivity (1–specicity) = TP (TP+FN) = FP (FP+TN) ÷ expresses how many times more likely people with the condition are to receive a positive test result compared to those who do not have the condition, while the negative likelihood ratio LR– (1–sensitivity) (specicity) = FN (TP+FN) = TN (FP+TN) ÷ expresses how likely it is that people with the condition will receive a negative test result compared to those who do not have the condition. 52. Methods Likelihood ratio Approximate* change in probability[12] Effect on posttest Probability of disease[13] Values between 0 and 1 decrease the probability of disease (-LR) 0.1 -45% Large decrease 0.2 -30% Moderate decrease 0.5 -15% Slight decrease 1 -0% None Values greater 1 increase the probability of disease (+LR) 1 +0% None 2 +15% Slight increase 5 +30% Moderate increase 10 +45% Large increase [12] McGee, Steven (1 August 2002). "Simplifying likelihood ratios". Journal of General Internal Medicine. 17 (8): 647–650. doi:10.1046/j.1525-1497.2002.10750.x. ISSN 0884-8734. PMC 1495095. PMID 12213147. [13] Henderson, Mark C.; Tierney, Lawrence M.; Smetana, Gerald W. (2012). The Patient History (2nd ed.). McGraw-Hill. p. 30. ISBN 978-0-07-162494-7. To graphically display the trade-off between sensitivity and specificity, we present the summary receiver operating characteristic (SROC) curve from the hierarchical summary receiver operating characteristic (HROC) model[4] and prediction region (i.e. for the forecast of the true sensitivity and specificity in a future study). We also plot the summary operating point and its confidence region. Forest plots for showing within-study estimates and confidence intervals for sensitivity and specificity separately. In the meta-analyses below, we have only included papers where we could calculate the numbers of true positive, false positives, true negatives and false negatives. For the other papers without this data, we have summarized their results qualitatively (i.e. without pooling). 63.1 PRISMA flow chart for anorectal syndromes 3. RESULTS In cl ud ed El ig ib ili ty Sc re en in g Id en tifi ca tio n Records identified through database searching (n = 14,551) Records after duplicates removed (n = 10,108) Titles/Abstracts screened (n = 10,108) Full-text articles assessed for eligibility (n = 33) Records excluded for irrelevant content (n = 10,075) Studies included in analysis (n = 8) Full-text articles excluded (n = 25) 12 No information about syndrome 9 No primary data 2 paper not found 73. Results 3.2 Anorectal syndrome • Country income level – 1/8 (13%) High income – 3/8 (38%) Upper Middle – 4/8 (50%) Lower Middle • Study population recruited from (may not add up to 100% because of multiple recruitment sites) – 5/8 (63%) Sexual health clinics – 1/8 (13%) Community setting (incl. bar, discos, CBOs) – 3/18 (38%) Unclear • Year of study – 2/8 (25%) 2009 and before – 3/8 (38%) 2010-2014 – 1/8 (13%) 2015 and after – 2/8 (25%) unclear 8 Web Annex F. Systematic review for syndromic management of the anorectal syndrome For detection of any STIs (chlamydia, gonorrhoea), four studies provided five estimates for pooling.[5-8] The pooled sensitivity for detecting chlamydia/gonorrhoea using a syndromic management approach is 32.4% (95% CI: 11.4-64.0), and pooled specificity is 81.7% (95% CI: 43.1-96.3). The diagnostic odds ratio is 2.13 (95% CI: 1.17-3.89). The positive likelihood ratio is 1.77 (95% CI: 0.94-3.31), and negative likelihood ratio is 0.83 (95% CI: 0.72-0.95). The inverse negative likelihood ratio is 1.21 (95% CI: 1.05-1.39). For a cohort of 1000 individuals: Prevalence Sensitivity Specificity PPV NPV Number of cases Missed cases False Positive (Overtreated) 0.05 0.324 0.817 0.085 0.958 50 34 174 0.1 0.324 0.817 0.164 0.916 100 68 165 0.15 0.324 0.817 0.238 0.873 150 101 156 0.2 0.324 0.817 0.307 0.829 200 135 146 0.25 0.324 0.817 0.371 0.784 250 169 137 0.3 0.324 0.817 0.431 0.738 300 203 128 0.35 0.324 0.817 0.488 0.692 350 237 119 0.4 0.324 0.817 0.541 0.644 400 270 110 0.45 0.324 0.817 0.592 0.596 450 304 101 0.5 0.324 0.817 0.639 0.547 500 338 92 0.55 0.324 0.817 0.684 0.497 550 372 82 0.6 0.324 0.817 0.726 0.446 600 406 73 0.65 0.324 0.817 0.767 0.394 650 439 64 0.7 0.324 0.817 0.805 0.341 700 473 55 0.75 0.324 0.817 0.842 0.287 750 507 46 0.8 0.324 0.817 0.876 0.232 800 541 37 0.85 0.324 0.817 0.909 0.176 850 575 27 0.9 0.324 0.817 0.941 0.118 900 608 18 0.95 0.324 0.817 0.971 0.060 950 642 9 1 0.324 0.817 1.000 0.000 1000 676 0 93. Results Se ns iti vi ty Specificity Study estimate 1 0 .8 .6 .4 .2 0 .2 .4 .6 .8 1 Summary point HSROC curve 95% confidence region 95% prediction region 10 Web Annex F. Systematic review for syndromic management of the anorectal syndrome De te ct io n of a ny S TI fo r t he a no re ct al s yn dr om e St ud y Ye ar o f st ud y Co un tr y Co un tr y in co m e le ve l Sa m pl e si ze W he re re cr ui te d Su b- po pu la ti on Ho w is a po si tiv e ca se de fin ed Pa th og en s / Te st Tr ue po si tiv e Fa ls e ne ga tiv e Fa ls e po si tiv e Tr ue ne ga tiv e M ug un du [5 ] 20 08 -2 00 9 In di a Lo w er m id dl e 86 8 Se xu al he al th c lin ic 10 0% M SM Re ce pt iv e an al s ex + /o r a na l di sc ha rg e + su bs eq ue nt pr oc to sc op y + /- sm ea r fin di ng s Ct /N g N AA T - Ro ch e Am pl ic or 53 74 25 0 49 1 M ug un du [5 ] 20 08 -2 00 9 In di a Lo w er m id dl e 86 8 Se xu al he al th c lin ic 10 0% M SM Ad di ng “ ris k as se ss m en t” to a bo ve 10 4 23 59 2 14 9 Q ui lte r[8 ] U nc le ar Ke ny a Lo w er m id dl e 69 8 Co m m un ity se tt in gs 99 % M SM An al sy m pt om s + “ ris k as se ss m en t” (M od el de riv ed ri sk sc or e) Ct /N g N AA T - Ab ot t Re al tim e 15 21 15 1 51 1 Re be [6 ] 20 12 So ut h Af ric a U pp er m id dl e 20 0 Se xu al he al th c lin ic 10 0% M SM Sy m pt om s on ly Ct /N g, Ap tim a Co m bo 2 9 38 13 14 0 Sa nd er s[ 7] 20 11 -2 01 2 Ke ny a Lo w er m id dl e 24 4 U nc le ar 10 0% M SM Sy m pt om s + “ ris k as se ss m en t” Ct /N g Ap tim a Co m bo 2 3 28 1 21 2 113. Results For detection of anal gonorrhoea, five studies provided five estimates for pooling.[6-10] The pooled sensitivity for detecting gonorrhoea using a syndromic management approach is 14.2% (95% CI: 6.1-29.7), and pooled specificity is 94.4% (95% CI: 84.8-98.1). The diagnostic odds ratio is 2.82 (95% CI: 1.08-7.40). The positive likelihood ratio is 2.56 (95% CI: 1.05-6.23), and the negative likelihood ratio is 0.91 (95% CI: 0.81-1.01). The inverse negative likelihood ratio is 1.10 (95% CI: 0.99-1.23). For a cohort of 1000 individuals: Prevalence Sensitivity Specificity PPV NPV Number of cases Missed cases False Positive (Overtreated) 0.05 0.142 0.944 0.118 0.954 50 43 53 0.1 0.142 0.944 0.220 0.908 100 86 50 0.15 0.142 0.944 0.309 0.862 150 129 48 0.2 0.142 0.944 0.388 0.815 200 172 45 0.25 0.142 0.944 0.458 0.767 250 215 42 0.3 0.142 0.944 0.521 0.720 300 257 39 0.35 0.142 0.944 0.577 0.671 350 300 36 0.4 0.142 0.944 0.628 0.623 400 343 34 0.45 0.142 0.944 0.675 0.574 450 386 31 0.5 0.142 0.944 0.717 0.524 500 429 28 0.55 0.142 0.944 0.756 0.474 550 472 25 0.6 0.142 0.944 0.792 0.423 600 515 22 0.65 0.142 0.944 0.825 0.372 650 558 20 0.7 0.142 0.944 0.855 0.320 700 601 17 0.75 0.142 0.944 0.884 0.268 750 644 14 0.8 0.142 0.944 0.910 0.216 800 686 11 0.85 0.142 0.944 0.935 0.163 850 729 8 0.9 0.142 0.944 0.958 0.109 900 772 6 0.95 0.142 0.944 0.980 0.055 950 815 3 1 0.142 0.944 1.000 0.000 1000 858 0 12 Web Annex F. Systematic review for syndromic management of the anorectal syndrome Se ns iti vi ty Specificity Study estimate 1 0 .8 .6 .4 .2 0 .2 .4 .6 .8 1 Summary point HSROC curve 95% confidence region 95% prediction region 133. Results De te ct io n of a na l g on or rh oe a fo r t he a no re ct al s yn dr om e St ud y Ye ar o f st ud y Co un tr y Co un tr y in co m e le ve l Sa m pl e si ze W he re re cr ui te d Su b- po pu la ti on Ho w is a po si tiv e ca se de fin ed Pa th og en s / Te st Tr ue po si tiv e Fa ls e ne ga tiv e Fa ls e po si tiv e Tr ue ne ga tiv e Ca ra ca s[ 9] 20 15 -1 6 Br az il Up pe r m id dl e 34 5 Un cle ar 10 0% Tr an sw om en Sy m pt om s on ly N ot re po rte d 4 43 26 27 2 Pa ss ar o[ 10 ] 20 12 -1 4 Pe ru Up pe r m id dl e 78 7 Un cle ar 10 0% M SM Sy m pt om s on ly N AA T 3 62 16 70 6 Q ui lte r[1 1] Un cle ar Ke ny a Lo w er m id dl e 69 8 Co m m un ity se tti ng s 99 % M SM An al sy m pt om s + “r isk as se ss m en t” (M od el de riv ed ri sk sc or e) 12 15 15 4 51 7 Re be [6 ] 20 12 So ut h Af ric a Up pe r m id dl e 20 0 Se xu al he al th cl in ic 10 0% M SM Sy m pt om s on ly 3 14 19 16 4 Sa nd er s[ 7] 20 11 -1 2 Ke ny a Lo w er m id dl e 19 Un cle ar 10 0% M SM Sy m pt om s + “r isk as se ss m en t” 4 3 11 1 14 Web Annex F. Systematic review for syndromic management of the anorectal syndrome There were no estimates found for evaluating the accuracy of syndromic management for herpes or syphilis. One study among MSM from sexual health clinics in the Netherlands provided an estimate for the sensitivity of syndromic management to detect LGV: 4.6% (95% CI: 1.3-11.4).[12] Studies with relevant information for evaluating anorectal syndrome • Caracas C, Jalil EM, Garcia ACF, Nazer SC, De Oliveira LP, Veloso V, et al. High chlamydia and gonorrhea prevalences and low performance of syndromic management among Brazilian transwomen. AIDS Research and Human Retroviruses. 2018;34 (Supplement 1):240. • Mugundu PR, Narayanan P, Das A, Morineau G. Assessing syndromic management algorithms for the diagnosis of rectal chlamydia and gonorrhoeae among MSM clinic attendees from two cities in India. Sexually Transmitted Infections. 2013;89(SUPPL. 1). • Okuku HS, Wahome E, Duncan S, Thiongo A, Mwambi J, Shafi J, et al. Evaluation of presumptive treatment recommendation for asymptomatic anorectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Journal of the International AIDS Society. 2012;15:99. • Passaro RC, Segura ER, Perez-Brumer A, Cabeza J, Montano SM, Lake JE, et al. Body Parts Matter: Social, Behavioral, and Biological Considerations for Urethral, Pharyngeal, and Rectal Gonorrhea and Chlamydia Screening Among MSM in Lima, Peru. Sexually Transmitted Diseases. 2018;45(9):607-14. • Quilter LAS, Obondi E, Kunzweiler C, Okall D, Bailey RC, Djomand G, et al. Prevalence and correlates of and a risk score to identify asymptomatic anorectal gonorrhoea and chlamydia infection among men who have sex with men in Kisumu, Kenya. Sexually Transmitted Infections. 2019;95(3):201-11. • Rebe K, Lewis D, Myer L, de Swardt G, Struthers H, Kamkuemah M, et al. A Cross Sectional Analysis of Gonococcal and Chlamydial Infections among Men-Who-Have-Sex-with-Men in Cape Town, South Africa. PLoS ONE. 2015;10(9):e0138315. • Sanders EJ, Wahome E, Okuku HS, Thiong'o AN, Smith AD, Duncan S, et al. Evaluation of WHO screening algorithm for the presumptive treatment of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Sexually Transmitted Infections. 2014;90(2):94-9. • Van der Bij AK, Spaargaren J, Morre SA, Fennema HS, Mindel A, Coutinho RA, et al. Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study. Clinical Infectious Diseases. 2006;42(2):186-94. 153. Results 3.3 Risk of Bias using QUADAS-2 Study Patient selection Index Test Reference standard Flow and Timing Mugundu[5] Low Low Low Low Quilter[8] Low Low Low Low Rebe[6] Low Low Low Low Sanders[7] Low Low Low Low Caracas[9] Low Low Unclear Low Passaro[10] Low Low Low Low 16 1. World Health Organization. (2021). Guidelines for the management of symptomatic sexually transmitted infections. World Health Organization. https://apps.who.int/iris/ handle/10665/342523. License: CC BY-NC-SA 3.0 IGO. 2. Cochrane Handbook for Systematic Reviews of Interventions version 5.1 [Available from: https://training.cochrane.org/handbook. 3. Joanna Briggs Institute Reviewer’s Manual. Diagnostic test accuracy systematic reviews. Appendix 9.1 Critical appraisal checklist [Available from: https://wiki.joannabriggs.org/ display/MANUAL/Appendix+9.1+Critical+appraisal+checklist. 4. Rutter CM, Gatsonis CA. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med. 2001;20(19):2865-84. 5. Mugundu PR, Narayanan P, Das A, Morineau G. Assessing syndromic management algorithms for the diagnosis of rectal chlamydia and gonorrhoeae among MSM clinic attendees from two cities in India. Sexually Transmitted Infections. 2013;89(SUPPL. 1). 6. Rebe K, Lewis D, Myer L, de Swardt G, Struthers H, Kamkuemah M, et al. A Cross Sectional Analysis of Gonococcal and Chlamydial Infections among Men-Who-Have-Sex- with-Men in Cape Town, South Africa. PLoS ONE. 2015;10(9):e0138315. 7. Sanders EJ, Wahome E, Okuku HS, Thiong'o AN, Smith AD, Duncan S, et al. Evaluation of WHO screening algorithm for the presumptive treatment of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Sexually Transmitted Infections. 2014;90(2):94-9. 8. Quilter LAS, Obondi E, Kunzweiler C, Okall D, Bailey RC, Djomand G, et al. Prevalence and correlates of and a risk score to identify asymptomatic anorectal gonorrhoea and chlamydia infection among men who have sex with men in Kisumu, Kenya. Sexually Transmitted Infections. 2019;95(3):201-11. 9. Caracas C, Jalil EM, Garcia ACF, Nazer SC, De Oliveira LP, Veloso V, et al. High chlamydia and gonorrhea prevalences and low performance of syndromic management among Brazilian transwomen. AIDS Research and Human Retroviruses. 2018;34 (Supplement 1):240. 10. 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Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature. Infect Dis Obstet Gynecol. 2016;2016:5758387. 18. Kent CK, Chaw JK, Wong W, Liska S, Gibson S, Hubbard G, et al. Prevalence of rectal, urethral, and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among men who have sex with men: San Francisco, California, 2003. Clin Infect Dis. 2005;41(1):67-74. 19. Soni S, White JA. Self-screening for Neisseria gonorrhoeae and Chlamydia trachomatis in the human immunodeficiency virus clinic--high yields and high acceptability. Sex Transm Dis. 2011;38(12):1107-9. 20. Turner AN, Reese PC, Ervin M, Davis JA, Fields KS, Bazan JA. HIV, rectal chlamydia, and rectal gonorrhea in men who have sex with men attending a sexually transmitted disease clinic in a midwestern US city. Sex Transm Dis. 2013;40(6):433-8. 21. Ross MW, Nyoni J, Ahaneku HO, Mbwambo J, McClelland RS, McCurdy SA. High HIV seroprevalence, rectal STIs and risky sexual behaviour in men who have sex with men in Dar es Salaam and Tanga, Tanzania. BMJ Open. 2014;4(8):e006175. 22. Kim EJ, Hladik W, Barker J, Lubwama G, Sendagala S, Ssenkusu JM, et al. Sexually transmitted infections associated with alcohol use and HIV infection among men who have sex with men in Kampala, Uganda. Sex Transm Infect. 2016;92(3):240-5. 23. Muraguri N, Tun W, Okal J, Broz D, Raymond HF, Kellogg T, et al. HIV and STI prevalence and risk factors among male sex workers and other men who have sex with men in Nairobi, Kenya. J Acquir Immune Defic Syndr. 2015;68(1):91-6. 18 Web Annex F. Systematic review for syndromic management of the anorectal syndrome 24. Katz DA, Dombrowski JC, Bell TR, Kerani RP, Golden MR. HIV Incidence Among Men Who Have Sex With Men After Diagnosis With Sexually Transmitted Infections. Sex Transm Dis. 2016;43(4):249-54. 25. Rowley J, Vander Hoorn S, Korenromp E, Low N, Unemo M, Abu-Raddad LJ, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019;97(8):548-62P. 26. Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, et al. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742-50. 27. Ong JJ, Baggaley RC, Wi TE, Tucker JD, Fu H, Smith MK, et al. Global Epidemiologic Characteristics of Sexually Transmitted Infections Among Individuals Using Preexposure Prophylaxis for the Prevention of HIV Infection: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019;2(12):e1917134. 28. Okuku HS, Wahome E, Duncan S, Thiongo A, Mwambi J, Shafi J, et al. Evaluation of presumptive treatment recommendation for asymptomatic anorectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Journal of the International AIDS Society. 2012;15:99. 19 5.1 Anorectal syndromes The search retrieved a total of 14,551 results. 4443 (31%) were identified as duplicates. The number of results pre-and post-deduplication is listed in the table below. Database name Diagnostic accuracy: Total number of results Diagnostic accuracy: Number of results once duplicates removed Other papers: Total number of results Other papers: Number of results once duplicates removed Ovid SP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily 1910 1904 1032 1030 OvidSP Embase 4750 3584 2550 2009 OvidSP Global Health 1155 475 413 223 OvidSP Northern Light Life Sciences Conference Abstracts 62 31 78 39 Ebsco CINAHL Plus 532 106 476 202 Ebsco Africa-Wide Information 237 13 49 8 Clarivate Analytics Web of Science Core Collection 896 220 332 99 BIREME/PAHO/WHO Virtual Health Library LILACS 47 44 32 31 Total 9589 6377 4962 3731 5. APPENDIX A - SEARCH RESULTS For more information, contact: World Health Organization Department of Global HIV, Hepatitis and STI Programme 20, avenue Appia 1211 Geneva 27 Switzerland Email: hiv-aids@who.int www.who.int/hiv

JUNE 2021 GUIDELINES FOR THE MANAGEMENT OF SYMPTOMATIC SEXUALLY TRANSMITTED INFECTIONS WEB ANNEX F. SYSTEMATIC REVIEW FOR SYNDROMIC MANAGEMENT OF THE ANORECTAL SYNDROME JUNE 2021 WEB ANNEX F. SYSTEMATIC REVIEW FOR SYNDROMIC MANAGEMENT OF THE ANORECTAL SYNDROME GUIDELINES FOR THE MANAGEMENT OF SYMPTOMATIC SEXUALLY TRANSMITTED INFECTIONS Guidelines for the management of symptomatic sexually transmitted infections: Web Annex F. Systematic review for syndromic management of the anorectal syndrome ISBN 978-92-4-003483-9 (electronic version) © World Health Organization 2021 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/ licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (http://www.wipo.int/amc/en/ mediation/rules/). Suggested citation. Guidelines for the management of symptomatic sexually transmitted infections: Web Annex F. Systematic review for syndromic management of the anorectal syndrome. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris. Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/ about/licensing. Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third-party-owned component in the work rests solely with the user. General disclaimers. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. This publication forms part of the WHO guideline entitled Guidelines for the management of symptomatic sexually transmitted infections. It is being made publicly available for transparency purposes and information, in accordance with the WHO handbook for guideline development, 2nd edition (2014). Design and layout by 400 Communications. iii CONTENTS 1. Introduction 1 2. Methods 2 3. Results 6 3.1 PRISMA flow chart for anorectal syndromes 6 3.2 Anorectal syndrome 7 3.3 Risk of Bias using QUADAS-2 15 4. References 16 5. Appendix A - Search Results 19 5.1 Anorectal syndromes 19 11. INTRODUCTION Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), continue to present significant health, social, and economic problems in the developing world, leading to considerable morbidity, mortality, and stigma. In under-resourced settings, the lack of adequate laboratory infrastructure and/or high prohibitive costs of diagnostics means that in many settings, STI management relies on syndromic management rather than aetiological diagnosis and management. In these settings, the detection of asymptomatic STIs is largely non-existent. Therefore, synthesizing the latest evidence for the performance of syndromic STI case management would help the World Health Organization (WHO) in their guideline recommendations for syndromic STI management, last updated in 2003.[1] To evaluate if there is still a role for syndromic STI management or whether STI diagnostics are critical for STI case management, we systematically reviewed the evidence for the performance of syndromic management of STIs. Specifically, we conducted reviews on the diagnostic accuracy and aetiologies of syndromic case management of genital ulcer, anorectal infection and lower abdominal pain. Our specific objectives were to review the flowcharts used for: • people presenting with genital ulcer disease to detect herpes simplex virus (HSV) or syphilis or lymphogranuloma venereum (LGV) or chancroid, or if no flowcharts found, a minor review of test accuracy of different tests, or risk association/prevalence. • people presenting with the anorectal syndrome to detect anal STIs or if no flowcharts found, a major review of test accuracy of different tests, or risk association/prevalence. • people presenting with lower abdominal pain to detect pelvic inflammatory disease (PID) or vaginal or cervical infections, or if no flowcharts found, a major review of test accuracy of different tests, or risk association/prevalence. 2Study inclusion • Clinical guidelines/algorithms – Flow charts for genital ulcer (for syphilis, HSV, LGV, chancroid), anorectal syndromes (for Ct/Ng/Mg/LGV/HSV/Tp/Donovanosis), lower abdominal pain (for PID, vaginal/cervical infections), and vaginal discharge • Randomized controlled trials • Observational studies • Report on at least one of: – Comparing syndromic case management against laboratory-confirmed STIs – Risk factor analysis of signs/symptoms associated with STI diagnoses and other risk factors associated with STI syndromes Study exclusion • Contains no original data i.e. systematic reviews/Letter/editorials/Commentaries/Book chapters – But can use these to identify other relevant primary studies • Qualitative research about outcomes • Duplicated results from another study • Laboratory studies about testing STI diagnostic performance • Studies restricting study population, e.g. men with urethritis, women with cervicitis Search method Three separate searches were conducted: one for each of the syndromes under investigation. We included papers that focused on other aspects of syndromic management (i.e. acceptability, feasibility, equity, resources) in addition to the accuracy or sensitivity of the syndromic management approach. The search for each syndrome has been constructed as below. • Concept 1: syndromic management • Concept 2: syndrome under investigation • Concept 3: diagnostic accuracy and sensitivity papers • Results group 1: concept 1 AND concept 2 AND concept 3 • Results group 2: (concept 1 AND concept 2) NOT Results group 1 2. METHODS 32. Methods A draft search strategy was compiled in the OvidSP Medline database by an experienced information specialist. The search strategy included strings of terms, synonyms and controlled vocabulary terms (where available). As the syndromic management approach was not introduced until 1996, the search was limited to papers published in 1995 or after. No other limits were added. This search strategy was refined with the project team until the results retrieved reflected the scope of the project. The agreed OvidSP Medline search was adapted for each database to incorporate database-specific syntax and controlled vocabularies. Full details of the search strings used for each database can be found in the appendix. A The following databases were searched on 12 and 13 September 2019. • Ovid SP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, 1946 to September 11, 2019 • OvidSP Embase, 1974 to 11 September 2019 • OvidSP Global Health, 1910 to week 35, 2019 • OvidSP Northern Light Life Sciences Conference Abstracts, 2010 to Week 34, 2019 • Ebsco CINAHL Plus, complete database • Ebsco Africa-Wide Information, complete database • Clarivate Analytics Web of Science Core Collection, consisting of the following databases: – Science Citation Index Expanded (SCI-EXPANDED), 1970 - present – Social Sciences Citation Index (SSCI), 1970 - present – Arts & Humanities Citation Index (A&HCI), 1975 - present – Conference Proceedings Citation Index - Science (CPCI-S), 1990 - present – Conference Proceedings Citation Index - Social Science & Humanities (CPCI-SSH), 1990 - present – Emerging Sources Citation Index (ESCI), 2015 – present • BIREME/PAHO/WHO Virtual Health Library LILACS, complete database All citations identified by our searches were imported into EndNote X9 software. Duplicates were identified and removed using the method described on the LAS blog.1 4 Web Annex F. Systematic review for syndromic management of the anorectal syndrome Data extraction We followed the guidelines in the Cochrane Handbook 5.1.[2] Three groups of two independent reviewers screened the title and abstracts of unduplicated papers. Discrepancies in screening were resolved by a third reviewer (JO). Each team extracted relevant data from deduplicated full publications. Risk of bias assessment was conducted using the Joanna Briggs Institute Checklist for diagnostic studies.[3] Statistical analysis Diagnostic accuracy cannot be summarized by one measure as sensitivity and specificity are correlated. Therefore, we must choose hierarchical (multilevel) models that use a binomial data structure, i.e. we use a hierarchical logistic regression model in STATA 13.1. After pooling the studies, we report the sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio. The inverse of the negative likelihood ratio (1/LR-) can be used to compare with the positive likelihood ratio to indicate whether the positive or negative test result has a greater impact on the odds of disease. Likelihood ratios assess the probability or likelihood that the test result obtained would be expected in a person with the condition, compared to the probability or likelihood that the same result would be seen in a person without the condition. The positive likelihood ratio LR+ sensitivity (1–specicity) = TP (TP+FN) = FP (FP+TN) ÷ expresses how many times more likely people with the condition are to receive a positive test result compared to those who do not have the condition, while the negative likelihood ratio LR– (1–sensitivity) (specicity) = FN (TP+FN) = TN (FP+TN) ÷ expresses how likely it is that people with the condition will receive a negative test result compared to those who do not have the condition. 52. Methods Likelihood ratio Approximate* change in probability[12] Effect on posttest Probability of disease[13] Values between 0 and 1 decrease the probability of disease (-LR) 0.1 -45% Large decrease 0.2 -30% Moderate decrease 0.5 -15% Slight decrease 1 -0% None Values greater 1 increase the probability of disease (+LR) 1 +0% None 2 +15% Slight increase 5 +30% Moderate increase 10 +45% Large increase [12] McGee, Steven (1 August 2002). "Simplifying likelihood ratios". Journal of General Internal Medicine. 17 (8): 647–650. doi:10.1046/j.1525-1497.2002.10750.x. ISSN 0884-8734. PMC 1495095. PMID 12213147. [13] Henderson, Mark C.; Tierney, Lawrence M.; Smetana, Gerald W. (2012). The Patient History (2nd ed.). McGraw-Hill. p. 30. ISBN 978-0-07-162494-7. To graphically display the trade-off between sensitivity and specificity, we present the summary receiver operating characteristic (SROC) curve from the hierarchical summary receiver operating characteristic (HROC) model[4] and prediction region (i.e. for the forecast of the true sensitivity and specificity in a future study). We also plot the summary operating point and its confidence region. Forest plots for showing within-study estimates and confidence intervals for sensitivity and specificity separately. In the meta-analyses below, we have only included papers where we could calculate the numbers of true positive, false positives, true negatives and false negatives. For the other papers without this data, we have summarized their results qualitatively (i.e. without pooling). 63.1 PRISMA flow chart for anorectal syndromes 3. RESULTS In cl ud ed El ig ib ili ty Sc re en in g Id en tifi ca tio n Records identified through database searching (n = 14,551) Records after duplicates removed (n = 10,108) Titles/Abstracts screened (n = 10,108) Full-text articles assessed for eligibility (n = 33) Records excluded for irrelevant content (n = 10,075) Studies included in analysis (n = 8) Full-text articles excluded (n = 25) 12 No information about syndrome 9 No primary data 2 paper not found 73. Results 3.2 Anorectal syndrome • Country income level – 1/8 (13%) High income – 3/8 (38%) Upper Middle – 4/8 (50%) Lower Middle • Study population recruited from (may not add up to 100% because of multiple recruitment sites) – 5/8 (63%) Sexual health clinics – 1/8 (13%) Community setting (incl. bar, discos, CBOs) – 3/18 (38%) Unclear • Year of study – 2/8 (25%) 2009 and before – 3/8 (38%) 2010-2014 – 1/8 (13%) 2015 and after – 2/8 (25%) unclear 8 Web Annex F. Systematic review for syndromic management of the anorectal syndrome For detection of any STIs (chlamydia, gonorrhoea), four studies provided five estimates for pooling.[5-8] The pooled sensitivity for detecting chlamydia/gonorrhoea using a syndromic management approach is 32.4% (95% CI: 11.4-64.0), and pooled specificity is 81.7% (95% CI: 43.1-96.3). The diagnostic odds ratio is 2.13 (95% CI: 1.17-3.89). The positive likelihood ratio is 1.77 (95% CI: 0.94-3.31), and negative likelihood ratio is 0.83 (95% CI: 0.72-0.95). The inverse negative likelihood ratio is 1.21 (95% CI: 1.05-1.39). For a cohort of 1000 individuals: Prevalence Sensitivity Specificity PPV NPV Number of cases Missed cases False Positive (Overtreated) 0.05 0.324 0.817 0.085 0.958 50 34 174 0.1 0.324 0.817 0.164 0.916 100 68 165 0.15 0.324 0.817 0.238 0.873 150 101 156 0.2 0.324 0.817 0.307 0.829 200 135 146 0.25 0.324 0.817 0.371 0.784 250 169 137 0.3 0.324 0.817 0.431 0.738 300 203 128 0.35 0.324 0.817 0.488 0.692 350 237 119 0.4 0.324 0.817 0.541 0.644 400 270 110 0.45 0.324 0.817 0.592 0.596 450 304 101 0.5 0.324 0.817 0.639 0.547 500 338 92 0.55 0.324 0.817 0.684 0.497 550 372 82 0.6 0.324 0.817 0.726 0.446 600 406 73 0.65 0.324 0.817 0.767 0.394 650 439 64 0.7 0.324 0.817 0.805 0.341 700 473 55 0.75 0.324 0.817 0.842 0.287 750 507 46 0.8 0.324 0.817 0.876 0.232 800 541 37 0.85 0.324 0.817 0.909 0.176 850 575 27 0.9 0.324 0.817 0.941 0.118 900 608 18 0.95 0.324 0.817 0.971 0.060 950 642 9 1 0.324 0.817 1.000 0.000 1000 676 0 93. Results Se ns iti vi ty Specificity Study estimate 1 0 .8 .6 .4 .2 0 .2 .4 .6 .8 1 Summary point HSROC curve 95% confidence region 95% prediction region 10 Web Annex F. Systematic review for syndromic management of the anorectal syndrome De te ct io n of a ny S TI fo r t he a no re ct al s yn dr om e St ud y Ye ar o f st ud y Co un tr y Co un tr y in co m e le ve l Sa m pl e si ze W he re re cr ui te d Su b- po pu la ti on Ho w is a po si tiv e ca se de fin ed Pa th og en s / Te st Tr ue po si tiv e Fa ls e ne ga tiv e Fa ls e po si tiv e Tr ue ne ga tiv e M ug un du [5 ] 20 08 -2 00 9 In di a Lo w er m id dl e 86 8 Se xu al he al th c lin ic 10 0% M SM Re ce pt iv e an al s ex + /o r a na l di sc ha rg e + su bs eq ue nt pr oc to sc op y + /- sm ea r fin di ng s Ct /N g N AA T - Ro ch e Am pl ic or 53 74 25 0 49 1 M ug un du [5 ] 20 08 -2 00 9 In di a Lo w er m id dl e 86 8 Se xu al he al th c lin ic 10 0% M SM Ad di ng “ ris k as se ss m en t” to a bo ve 10 4 23 59 2 14 9 Q ui lte r[8 ] U nc le ar Ke ny a Lo w er m id dl e 69 8 Co m m un ity se tt in gs 99 % M SM An al sy m pt om s + “ ris k as se ss m en t” (M od el de riv ed ri sk sc or e) Ct /N g N AA T - Ab ot t Re al tim e 15 21 15 1 51 1 Re be [6 ] 20 12 So ut h Af ric a U pp er m id dl e 20 0 Se xu al he al th c lin ic 10 0% M SM Sy m pt om s on ly Ct /N g, Ap tim a Co m bo 2 9 38 13 14 0 Sa nd er s[ 7] 20 11 -2 01 2 Ke ny a Lo w er m id dl e 24 4 U nc le ar 10 0% M SM Sy m pt om s + “ ris k as se ss m en t” Ct /N g Ap tim a Co m bo 2 3 28 1 21 2 113. Results For detection of anal gonorrhoea, five studies provided five estimates for pooling.[6-10] The pooled sensitivity for detecting gonorrhoea using a syndromic management approach is 14.2% (95% CI: 6.1-29.7), and pooled specificity is 94.4% (95% CI: 84.8-98.1). The diagnostic odds ratio is 2.82 (95% CI: 1.08-7.40). The positive likelihood ratio is 2.56 (95% CI: 1.05-6.23), and the negative likelihood ratio is 0.91 (95% CI: 0.81-1.01). The inverse negative likelihood ratio is 1.10 (95% CI: 0.99-1.23). For a cohort of 1000 individuals: Prevalence Sensitivity Specificity PPV NPV Number of cases Missed cases False Positive (Overtreated) 0.05 0.142 0.944 0.118 0.954 50 43 53 0.1 0.142 0.944 0.220 0.908 100 86 50 0.15 0.142 0.944 0.309 0.862 150 129 48 0.2 0.142 0.944 0.388 0.815 200 172 45 0.25 0.142 0.944 0.458 0.767 250 215 42 0.3 0.142 0.944 0.521 0.720 300 257 39 0.35 0.142 0.944 0.577 0.671 350 300 36 0.4 0.142 0.944 0.628 0.623 400 343 34 0.45 0.142 0.944 0.675 0.574 450 386 31 0.5 0.142 0.944 0.717 0.524 500 429 28 0.55 0.142 0.944 0.756 0.474 550 472 25 0.6 0.142 0.944 0.792 0.423 600 515 22 0.65 0.142 0.944 0.825 0.372 650 558 20 0.7 0.142 0.944 0.855 0.320 700 601 17 0.75 0.142 0.944 0.884 0.268 750 644 14 0.8 0.142 0.944 0.910 0.216 800 686 11 0.85 0.142 0.944 0.935 0.163 850 729 8 0.9 0.142 0.944 0.958 0.109 900 772 6 0.95 0.142 0.944 0.980 0.055 950 815 3 1 0.142 0.944 1.000 0.000 1000 858 0 12 Web Annex F. Systematic review for syndromic management of the anorectal syndrome Se ns iti vi ty Specificity Study estimate 1 0 .8 .6 .4 .2 0 .2 .4 .6 .8 1 Summary point HSROC curve 95% confidence region 95% prediction region 133. Results De te ct io n of a na l g on or rh oe a fo r t he a no re ct al s yn dr om e St ud y Ye ar o f st ud y Co un tr y Co un tr y in co m e le ve l Sa m pl e si ze W he re re cr ui te d Su b- po pu la ti on Ho w is a po si tiv e ca se de fin ed Pa th og en s / Te st Tr ue po si tiv e Fa ls e ne ga tiv e Fa ls e po si tiv e Tr ue ne ga tiv e Ca ra ca s[ 9] 20 15 -1 6 Br az il Up pe r m id dl e 34 5 Un cle ar 10 0% Tr an sw om en Sy m pt om s on ly N ot re po rte d 4 43 26 27 2 Pa ss ar o[ 10 ] 20 12 -1 4 Pe ru Up pe r m id dl e 78 7 Un cle ar 10 0% M SM Sy m pt om s on ly N AA T 3 62 16 70 6 Q ui lte r[1 1] Un cle ar Ke ny a Lo w er m id dl e 69 8 Co m m un ity se tti ng s 99 % M SM An al sy m pt om s + “r isk as se ss m en t” (M od el de riv ed ri sk sc or e) 12 15 15 4 51 7 Re be [6 ] 20 12 So ut h Af ric a Up pe r m id dl e 20 0 Se xu al he al th cl in ic 10 0% M SM Sy m pt om s on ly 3 14 19 16 4 Sa nd er s[ 7] 20 11 -1 2 Ke ny a Lo w er m id dl e 19 Un cle ar 10 0% M SM Sy m pt om s + “r isk as se ss m en t” 4 3 11 1 14 Web Annex F. Systematic review for syndromic management of the anorectal syndrome There were no estimates found for evaluating the accuracy of syndromic management for herpes or syphilis. One study among MSM from sexual health clinics in the Netherlands provided an estimate for the sensitivity of syndromic management to detect LGV: 4.6% (95% CI: 1.3-11.4).[12] Studies with relevant information for evaluating anorectal syndrome • Caracas C, Jalil EM, Garcia ACF, Nazer SC, De Oliveira LP, Veloso V, et al. High chlamydia and gonorrhea prevalences and low performance of syndromic management among Brazilian transwomen. AIDS Research and Human Retroviruses. 2018;34 (Supplement 1):240. • Mugundu PR, Narayanan P, Das A, Morineau G. Assessing syndromic management algorithms for the diagnosis of rectal chlamydia and gonorrhoeae among MSM clinic attendees from two cities in India. Sexually Transmitted Infections. 2013;89(SUPPL. 1). • Okuku HS, Wahome E, Duncan S, Thiongo A, Mwambi J, Shafi J, et al. Evaluation of presumptive treatment recommendation for asymptomatic anorectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Journal of the International AIDS Society. 2012;15:99. • Passaro RC, Segura ER, Perez-Brumer A, Cabeza J, Montano SM, Lake JE, et al. Body Parts Matter: Social, Behavioral, and Biological Considerations for Urethral, Pharyngeal, and Rectal Gonorrhea and Chlamydia Screening Among MSM in Lima, Peru. Sexually Transmitted Diseases. 2018;45(9):607-14. • Quilter LAS, Obondi E, Kunzweiler C, Okall D, Bailey RC, Djomand G, et al. Prevalence and correlates of and a risk score to identify asymptomatic anorectal gonorrhoea and chlamydia infection among men who have sex with men in Kisumu, Kenya. Sexually Transmitted Infections. 2019;95(3):201-11. • Rebe K, Lewis D, Myer L, de Swardt G, Struthers H, Kamkuemah M, et al. A Cross Sectional Analysis of Gonococcal and Chlamydial Infections among Men-Who-Have-Sex-with-Men in Cape Town, South Africa. PLoS ONE. 2015;10(9):e0138315. • Sanders EJ, Wahome E, Okuku HS, Thiong'o AN, Smith AD, Duncan S, et al. Evaluation of WHO screening algorithm for the presumptive treatment of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Sexually Transmitted Infections. 2014;90(2):94-9. • Van der Bij AK, Spaargaren J, Morre SA, Fennema HS, Mindel A, Coutinho RA, et al. Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study. Clinical Infectious Diseases. 2006;42(2):186-94. 153. Results 3.3 Risk of Bias using QUADAS-2 Study Patient selection Index Test Reference standard Flow and Timing Mugundu[5] Low Low Low Low Quilter[8] Low Low Low Low Rebe[6] Low Low Low Low Sanders[7] Low Low Low Low Caracas[9] Low Low Unclear Low Passaro[10] Low Low Low Low 16 1. World Health Organization. (2021). Guidelines for the management of symptomatic sexually transmitted infections. World Health Organization. https://apps.who.int/iris/ handle/10665/342523. License: CC BY-NC-SA 3.0 IGO. 2. Cochrane Handbook for Systematic Reviews of Interventions version 5.1 [Available from: https://training.cochrane.org/handbook. 3. Joanna Briggs Institute Reviewer’s Manual. Diagnostic test accuracy systematic reviews. Appendix 9.1 Critical appraisal checklist [Available from: https://wiki.joannabriggs.org/ display/MANUAL/Appendix+9.1+Critical+appraisal+checklist. 4. Rutter CM, Gatsonis CA. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med. 2001;20(19):2865-84. 5. Mugundu PR, Narayanan P, Das A, Morineau G. Assessing syndromic management algorithms for the diagnosis of rectal chlamydia and gonorrhoeae among MSM clinic attendees from two cities in India. Sexually Transmitted Infections. 2013;89(SUPPL. 1). 6. Rebe K, Lewis D, Myer L, de Swardt G, Struthers H, Kamkuemah M, et al. A Cross Sectional Analysis of Gonococcal and Chlamydial Infections among Men-Who-Have-Sex- with-Men in Cape Town, South Africa. PLoS ONE. 2015;10(9):e0138315. 7. Sanders EJ, Wahome E, Okuku HS, Thiong'o AN, Smith AD, Duncan S, et al. Evaluation of WHO screening algorithm for the presumptive treatment of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Sexually Transmitted Infections. 2014;90(2):94-9. 8. Quilter LAS, Obondi E, Kunzweiler C, Okall D, Bailey RC, Djomand G, et al. Prevalence and correlates of and a risk score to identify asymptomatic anorectal gonorrhoea and chlamydia infection among men who have sex with men in Kisumu, Kenya. Sexually Transmitted Infections. 2019;95(3):201-11. 9. Caracas C, Jalil EM, Garcia ACF, Nazer SC, De Oliveira LP, Veloso V, et al. High chlamydia and gonorrhea prevalences and low performance of syndromic management among Brazilian transwomen. AIDS Research and Human Retroviruses. 2018;34 (Supplement 1):240. 10. 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Journal of the International AIDS Society. 2012;15:99. 19 5.1 Anorectal syndromes The search retrieved a total of 14,551 results. 4443 (31%) were identified as duplicates. The number of results pre-and post-deduplication is listed in the table below. Database name Diagnostic accuracy: Total number of results Diagnostic accuracy: Number of results once duplicates removed Other papers: Total number of results Other papers: Number of results once duplicates removed Ovid SP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily 1910 1904 1032 1030 OvidSP Embase 4750 3584 2550 2009 OvidSP Global Health 1155 475 413 223 OvidSP Northern Light Life Sciences Conference Abstracts 62 31 78 39 Ebsco CINAHL Plus 532 106 476 202 Ebsco Africa-Wide Information 237 13 49 8 Clarivate Analytics Web of Science Core Collection 896 220 332 99 BIREME/PAHO/WHO Virtual Health Library LILACS 47 44 32 31 Total 9589 6377 4962 3731 5. APPENDIX A - SEARCH RESULTS For more information, contact: World Health Organization Department of Global HIV, Hepatitis and STI Programme 20, avenue Appia 1211 Geneva 27 Switzerland Email: hiv-aids@who.int www.who.int/hiv